Determinants of susceptibility/resistance and natural history of L. major infection in endemic foci include environmental and host related risk factors. Our long term goal is to elucidate the natural history of L. major infection and to weight the relative importance of host related risk factors of cutaneous leishmaniasis (CL) emergence and severity considering the confounding effect of environmental factors influencing exposure. The specific hypothesis is that the natural history of L. major infection and the clinical expression of cutaneous leishmaniasis varies according to past history of transmission and to the type of biotope in the study area. Host related immunological surrogates of protection other than leishmanin skin test (LSI)prior to transmission might explain resistance to the disesase and might be used as efficacy criteria in the context of vaccines'evaluation in the field. Based on these observations the focus of project 1 is to refine bya prospective cohort population based study the estimation of the epidemetric parameters and clinical description of disease and transmission dynamics to improve the understanding of natural history of Leishmania (L.)major infection and its determinants. The specific aims are to: 1. Elucidate epidemetric parameters of L. major infection. We will use leishmanin skin test (LST) and clinical observations, the incidence of CL versus asymptomatic infection (LST+/lesions-) in a two years prospective study in order to determine: i) the prevalence of LST positivity, ii) the rate of conversion and reversion of LST, iii)the incidence of symptomatic/ asymptomatic infection, iv) the score severity of disease, v) the rate of recurrence, vi) the predictive value and the protection fraction of LST positivity. 2. To evaluate the relative importance of immune host related factors and environmental on the natural history and clinical expression of the disease. These include LST, cytotoxic immune response and antibodies against sand flies'saliva antigens, distance to colonized area by reservoirs, characteristics of dwelling and its compound, socio-economic factors and pathogenic properties of L. major isolates. 3. To develop and validate scales for severity of cutaneous lesions and quality of resulting scars. The scale items include size of the ulcer, color (hypopigmentation, hyperpigmentation, normal skin) and height.